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Applied Math Seminar: Conformational changes at the nucleotide site of myosin and kinesin motors
4:10 PM, Webster B8
ABSTRACT: The hydrolysis of ATP provides the free energy for the generation of biologically useful motion by kinesin and myosin motor proteins. Angstrom magnitude conformational changes at the nucleotide site associated with hydrolysis are propagated to peripheral elements of the proteins where they are amplified into nanometer size steps of motion. How this occurs remains unexplained. Resolution of the mechanism will require understanding the sequence of protein conformational changes that are involved. We have used electron paramagnetic resonance spectroscopy to probe conformational changes at the ATP binding site of kinesin and myosin motors. Myosin translocates along actin filaments. Kinesin moves along microtubules. Our results show that the closed nucleotide site seen in myosin x-ray structures opens when myosin binds strongly to actin. Conversely, the open nucleotide site seen in kinesin x-ray structures closes when kinesin binds to microtubules. The two motors have evolved from a common ancestor protein, and the distinct open/closed x-ray structures of each appear to be additionally capturing a conformation of the other. Molecular dynamics simulations are used to better understand the spectroscopic observations in terms of available x-ray structures and homologies between the two classes of motors. The results provide structural explanations for relationships between the isolated motor biochemical cycles and functioning mechanical cycles. Additionally, the results fill in gaps in the crystallographic observations of the motor proteins.